Project Details
Projekt
Development of a fluorinated PET tracer for imaging of sigma-2 receptors in the brain and in brain tumors
Subject Area
Pharmacy
Term
from 2015 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 277977652
It was shown that sigma-2 receptors are highly expressed in regions of the central nervous system, which control motoric behavior. Animal models revealed the involvement of sigma-2 receptors in movement disorders, depression and anxiety. It was postulated that sigma-2 receptors contribute to some of the motoric side effects of typical antipsychotics. Very importantly, the sigma-2 receptor is highly expressed in several human tumor cell lines. Therefore molecular imaging of the sigma-2 receptor in the central nervous system and, in particular, in brain tumors represents an important modality for the validation of the sigma-2 receptor as drug target, for quantification of the sigma-2 receptor in healthy and pathological conditions and for tumor diagnosis.In this project a fluorinated PET tracer for imaging of sigma-2 receptors in the human brain will be developed. At present, a suitable radiotracer for clinical sigma-2 receptor imaging with PET is not available. The identification, development and evaluation of a suitable molecule to selectively address the sigma-2 receptor is scientifically challenging, since in an iterative process affinity, selectivity, chemical stability, lipophilicity including brain uptake, distribution, biotransformation, and radiochemical availability have to be considered. Based on our experience with the development of [18F]-(S)-fluspidine, a fluorinated PET tracer for imaging of sigma-1 receptors in the brain, we aim at - the synthesis of a fluorinated sigma-2 ligand with high sigma-2 affinity, selectivity and appropriate pharmacokinetic properties, -a reproducible and high yielding radiosynthesis and - the biological evaluation of the fluorinated PET tracer in vitro and in vivo.
DFG Programme
Research Grants
